Sign Out
Hypersensitivity Reactions: Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in less than 1% of subjects receiving dolutegravir in Phase 3 clinical trials. Discontinue dolutegravir and other suspect agents immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping treatment with dolutegravir or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction. Dolutegravir is contraindicated in patients who have experienced a previous hypersensitivity reaction to dolutegravir.
Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C Co-infection: Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of dolutegravir [see Adverse Reactions]. In some cases the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation particularly in the setting where anti-hepatitis therapy was withdrawn. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with dolutegravir are recommended in patients with underlying hepatic disease such as hepatitis B or C.
Fat Redistribution: Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
Immune Reconstitution Syndrome: Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including dolutegravir. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment.
Hepatic Impairment: No clinically important pharmacokinetic differences between subjects with moderate hepatic impairment and matching healthy subjects were observed. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh Score A or B). The effect of severe hepatic impairment (Child-Pugh Score C) on the pharmacokinetics of dolutegravir has not been studied. Therefore, dolutegravir is not recommended for use in patients with severe hepatic impairment [see Pharmacology under Actions].
Renal Impairment: Dolutegravir plasma concentrations were decreased in subjects with severe renal impairment compared with those in matched healthy controls. However, no dosage adjustment is necessary for treatment-naïve or treatment-experienced and INSTI-naïve patients with mild, moderate, or severe renal impairment or for INSTI- experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance) with mild or moderate renal impairment. Caution is warranted for INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance [see Pharmacology: Microbiology under Actions]) with severe renal impairment, as the decrease in dolutegravir concentrations may result in loss of therapeutic effect and development of resistance to dolutegravir or other coadministered antiretroviral agents [see Pharmacology under Actions]. Dolutegravir has not been studied in patients on dialysis.
Use in Children: The safety, virologic, and immunologic responses in subjects who received dolutegravir were evaluated in 46 treatment-experienced, INSTI-naïve, HIV-1-infected subjects aged 6 to less than 18 years in an open-label, multicenter, dose-finding clinical trial, IMPAACT P1093 [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Frequency, type, and severity of adverse drug reactions among the 46 pediatric subjects were comparable to those observed in adults [see Adverse Reactions]. In 17 subjects weighing at least 30 kg, pharmacokinetic parameters of dolutegravir were comparable to adults receiving 50 mg once daily [see Pharmacology under Actions].
Safety and efficacy of dolutegravir have not been established in pediatric patients weighing less than 30 kg or in any pediatric patients who are INSTI-experienced.
Use in Elderly: Clinical trials of dolutegravir did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, caution should be exercised in the administration of dolutegravir in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Pharmacology under Actions].
